Cited by 1,271Neurogenesis and neuroplasticity mechanismsCancer-related cognitive impairment studiesEffects of Radiation Exposure

Irradiation induces neural precursor-cell dysfunction

Monje, Michelle L., Mizumatsu, Shinichiro, Fike, John R., Palmer, Theo D.·2002·Nature Medicine

Abstract

In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions.

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Crossref · 10.1038/nm749

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Authors
Monje, M. L., Mizumatsu, S., Fike, J. R., & Palmer, T. D.
Affiliations
  • Stanford Medicine (US)
  • University of California, San Francisco (US)
  • Stanford University (US)
Venue
Nature Medicine
Published
2002-08-05
Volume
8
Issue
9
Pages
955-962
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2098137179
Cited by
1,271
References
35
Citations by year
2026: 26 · 2025: 63 · 2024: 48 · 2023: 43 · 2022: 57 · 2021: 67 · 2020: 60 · 2019: 52 · 2018: 43 · 2017: 64 · 2016: 62 · 2015: 64 · 2014: 62 · 2013: 65 · 2012: 58
FWCI
8.41
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute of Mental Health (MH20016-05)
  • National Cancer Institute (R01CA076141)
  • National Institute of Neurological Disorders and Stroke (R01NS40088)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
Keywords
cranial irradiation, radiation-induced cognitive impairment, hippocampal neurogenesis, neural progenitor cells, postnatal neurogenesis, angiogenesis, microglial activation, pediatric brain tumors, radiotherapy complications
MeSH terms
Animals, Astrocytes, Brain, Bromodeoxyuridine, Cell Differentiation, Cell Division, Cells, Cultured, DNA Repair, Female, Neovascularization, Pathologic, Neurons, Rats, Inbred F344, Stem Cells, Microglia, Cell Transplantation, Stem Cell Transplantation, Rats

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